Single-dose zanzalintinib testing in people with moderate liver impairment

A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Zanzalintinib in Participants With Moderate Hepatic Impairment

This will test how one dose of zanzalintinib behaves in the blood of people with moderate liver impairment compared with healthy people.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Exelixis (Industry-sponsored)
• Drugs / interventions: zanzalintinib
• Locations: 2 sites (Orlando, Florida and 1 other locations)
• Trial ID: NCT06962332 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional study gives a single dose of zanzalintinib and measures plasma pharmacokinetics in participants with moderate hepatic impairment versus matched healthy volunteers. Participants with moderate impairment are defined by Child-Pugh Class B (score 7–9) and must otherwise have no clinically significant medical history and meet bone marrow and smoking restrictions. Serial blood samples are collected after dosing to characterize absorption, distribution, metabolism, and elimination parameters, while safety is monitored. The trial is conducted at two Exelixis clinical sites in Orlando, FL and San Antonio, TX.

Who should consider this trial

Good fit: Adults with moderate hepatic impairment (Child-Pugh Class B, score 7–9) who are otherwise in good health, meet bone marrow and smoking limits, and can attend in-person dosing and PK sampling visits.

Not a fit: People with severe or only mild liver impairment, significant other medical illnesses, recent blood or plasma donors, or those unable to comply with smoking or visit requirements are unlikely to benefit.

Why it matters

Potential benefit: If successful, the results could help determine safe dosing recommendations for zanzalintinib in patients with moderate liver impairment.

How similar studies have performed: Pharmacokinetic studies in patients with hepatic impairment are a standard, well-established approach and have previously informed safe dosing for many medications.

Eligibility criteria

Key Inclusion Criteria:

* All Participants:

  * No clinically significant medical history (aside from the HI for participants in the HI group only), physical examination findings, or vital signs, as deemed by the investigator.
  * A continuous non-smoker or moderate smoker who smokes ≤ 10 cigarettes, ≤ 2 cigars, or ≤2 pipes per day and agree to limit smoking during the confinement period to ≤ 4 cigarettes or ≤1 cigar or pipe per day. Participant must agree to maintain the same smoking status (smoker or non-smoker) from screening and until after the last PK sample collection.
  * Has not donated blood within 30 days of dosing or plasma within 7 days of dosing and must agree to refrain from blood donation until at least 30 days following dosing.
* Participants with Moderate HI Only:

  * Adequate bone marrow function, at the screening and dosing visit.
  * Is classified as having moderate HI by the Child-Pugh classification system (Class B, score of 7 to 9, inclusive) and has a total bilirubin value within the range of \> 1.5\* upper limit of normal (ULN) and ≤ 3\* ULN at the screening and dosing visit.
  * Has a diagnosis of chronic (\> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency at the screening visit with features of cirrhosis due to any etiology.
* Healthy Control Participants Only:

  * Age must be within ± 10 years of the mean age of participants with moderate HI. The sex ratio (male/female ratio), and smoking status ratio (smokers/non-smokers ratio) must be the same to the sex and smoking status ratio of participants with moderate HI.

Key Exclusion Criteria:

* All Participants:

  * • History of any medical or surgical conditions that would potentially alter absorption, distribution, metabolism, and/or excretion of orally administered drugs.
  * Has or is at risk for major cardiac events or dysfunction.
* Participants with Moderate HI Only:

  * History of liver or other solid organ transplant.
  * Fluctuating or rapidly deteriorating hepatic function (the definition of the change of more than 1 Child-Pugh point) within 30 days prior to Day 1, in the opinion of the investigator and Sponsor.
  * Symptoms or history of Grade 3 or worse degree of encephalopathy within 3 months of dosing.
  * Clinical evidence of severe ascites at the screening visit or at check in.
* Healthy Control Participants Only:

  * History or presence of alcohol or drug abuse within the past 2 years prior to dosing.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Where this trial is running

Orlando, Florida and 1 other locations

• Exelixis Clinical Site #1 — Orlando, Florida, United States (Recruiting)
• Exelixis Clinical Site #2 — San Antonio, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Exelixis Clinical Trials

Conditions Hepatic Impairment; Moderate Hepatic Impairment; Zanzalintinib; Pharmacokinetics